This is a new submission for a K24 Midcareer Investigator Award in Patient-Oriented Research. The overarching objective of this proposal is to allow the Candidate, Warren D. Taylor, MD, to 1) develop expertise in PET imaging and 2) obtain skills and experience in mentoring junior researchers. This will extend his past work examining biomarkers of clinical outcomes in depression into cellular and molecular measures while mentoring new investigators on biomarker approaches examining important clinical outcomes. To achieve these goals, the Career Development Plan provides for training in PET imaging methodology, methods for analyzing PET imaging data, and methods for multimodal imaging analyses combining PET and MRI data. His mentorship skills will be enhanced through by serving as faculty for local and national mentoring workshops, formal training, and work to develop a research training program. Supporting these goals, the Mentoring Plan focuses on junior investigators in patient-oriented research with interests in depression. Utilizing multiple Vanderbilt resources to identify and support these trainees, the Candidate will provide hands-on training in research methodology with the goal of trainees preparing publishable scientific reports and entry-level grant applications. Extensive institutional resources at Vanderbilt will augment experiences provided by the Candidate. Finally, the Candidate's career development focus on developing expertise in PET imaging will be facilitated by the Research Plan. This pilot project involves obtaining florbetapir (18F) PET data in older adults with depression with the overarching aim of investigating the role of amyloid deposition on cognition and antidepressant outcomes. This project is linked to the Candidate's current R01, a study examining structural and functional MRI biomarkers influencing antidepressant treatment outcomes. By acquiring data on amyloid binding in 33 cognitively intact but depressed individuals, this project will test the hypotheses that increased amyloid binding is associated with poorer cognitive performance and poorer response to 8 weeks of blinded escitalopram. By integrating the PET data with MRI data, we will also examine whether this effect is related to early amyloid deposition in default mode network regions, and whether amyloid deposition is associated with altered network functional connectivity. Overall, this award will provide crucial support for the Candidate to expand his research expertise and mentoring programs. It will also provide novel information on the effects of Alzheimer neuropathology on late-life depression outcomes that will guide future proposals.